Allergic asthma is one of the most common diseases worldwide, resulting in a burden of diseases. No available therapeutic regimens can cure asthma thus far.

We sought to identify new molecular targets for T_H9 cell–mediated allergic airway inflammation.

Wild-type p53-induced phosphatase 1 (Wip1) gene knockout mice, Wip1 inhibitor–treated mice, and ovalbumin-induced allergic airway inflammation mouse models were used to characterize the roles of Wip1 in allergic airway inflammation. The induction of T_H cell subsets in vitro, real-time PCR, immunoblots, luciferase assays, and chromatin immunoprecipitation assays were used to determine the regulatory pathways of Wip1 in T_H9 differentiation.

Here we demonstrate that Wip1-deficient mice are less prone to allergic airway inflammation, as indicated by the decreased pathologic alterations in lungs. Short-term treatment with a Wip1-specific inhibitor significantly ameliorates allergic inflammation progression. Intriguingly, Wip1 selectively impaired T_H9 but not T_H1, T_H2, and T_H17 cell differentiation. Biochemical assays show that Wip1 deficiency increases c-Jun/c-Fos activity in a c-Jun N-terminal kinase–dependent manner and that c-Jun/c-Fos directly binds to Il9 promoter and inhibits Il9 transcription.

Wip1 controls T_H9 cell development through regulating c-Jun/c-Fos activity on the Il9 promoter and is important for the pathogenesis of allergic airway inflammation. These findings shed light on the previously unrecognized roles of Wip1 in T_H9 cell differentiation. The inhibitory effects of a Wip1 inhibitor on the pathogenesis of allergic airway inflammation can have important implications for clinical application of Wip1 inhibitors in allergy therapies.